Identification of a new type of monocytic cell that promotes affinity maturation and characterization of its B cell-activation mechanism

• Project/Area Number: 24560961
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biofunction/Bioprocess
• Research Institution: Okayama University
• Principal Investigator: OHMORI HITOSHI 岡山大学, 自然科学研究科, 教授 (70116440)
• Co-Investigator(Renkei-kenkyūsha): MAGARI Masaki 岡山大学, 大学院自然科学研究科, 助教 (50359882)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 濾胞樹状細胞 / 単球系細胞分化 / CSF-1受容体 / IL-34 / CSF-1 / 細胞情報伝達 / 胚中心B細胞 / マイクロRNA / 胚中心B 細胞 / 単球系細胞 / 胚中心Ｂ細胞 / ＣＳＦ－１受容体 / シグナル伝達 / RNAi / 胚中心 / 抗体 / Ｂ細胞 / 親和性成熟 / 骨髄系細胞

Outline of Final Research Achievements

B cells differentiate into high-afffinity antibody producers as the consequence of hypermutation immunoglobulin genes followed by selection of mutated clones. Follicular dendritic cells (FDCs) have been shown to play a pivotal role in these processes. To investigate immunologic functions of FDCs、we established an FDC line, FL-Y, which was shown to induce a new class of monocytic cells named FDMCs with a unique B cell stimulating activity. We found FDMC differentiation was strictly dependent on CSF-1 receptor (R) and the ligand, IL-34. This is the first report describing IL-34-selective CSF-1R signaling pathway.

Research Products

• [Journal Article] MicroRNA-100-5p indirectly modulates the expression of Il6, Ptgs1/2 and Tlr4 mRNA in the mouse follicular dendritic cell-like cell line, FL-Y. (2015)
  • Author(s): Aungier, S.R., Ohmori, H., Clinton, M., Mabbott, N.A.
  • Journal Title: Immunology Volume: 144 Issue: 1 Pages: 34-35
  • DOI: 10.1111/imm.12342
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CSF-1 receptor-mediated differentiation of a new type of monocytic cell with B cell-stimulating activity: its selective dependence on IL-34. (2014)
  • Author(s): Fumihiro Yamane
  • Journal Title: J Leukoc Biol Volume: 95 Issue: 1 Pages: 19-31
  • DOI: 10.1189/jlb.0613311
  • Peer Reviewed
• [Journal Article] 胚中心におけるＢ細胞のnegative selectionと濾胞樹状細胞 (2012)
  • Author(s): 曲 正樹、金山直樹、大森 齊
  • Journal Title: 臨床免疫・アレルギー科 Volume: 58 Pages: 259-265
• [Journal Article] 抗体遺伝子への突然変異機能を有するニワトリＢ細胞株の機能拡張によるin vitroモノクローナル抗体作製・改良システム (2012)
  • Author(s): 金山直樹、大森 齊
  • Journal Title: 細胞工学 Volume: 31 Pages: 1159-1165
• [Presentation] IL-34依存的に発生する新規単球系細胞の分化機構；濾胞樹状細胞によるIL-34特異的作用の解析 (2014)
  • Author(s): 小川紗也香，大森斉，曲正樹 他６名
  • Organizer: 第３７回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-12-01 – 2014-12-04
• [Presentation] Follicular dendritic cells induce a new class of myeloid cells with unique B cell stimulating activities: specific dependence on IL-34/CSF-1R signaling pathway. (2013)
  • Author(s): Yamane, F., Nishikawa, Y., Matsui, K., Asakura, M., Iwasaki, E., Watanabe, K., Tanimoto, H., Sano, H., Fujiwara, Y., Stanley, E. R., Kanayama, N., Mabbott, N. A., Magari, M., Ohmori, H.
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: ミラノ（イタリア）
• [Presentation] IL-34-dependent monocytic cells that promote centroblast-associated phenotype expression in mouse activated B cells (2012)
  • Author(s): 曲 正樹、大森 齊他９名
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 神戸国際会議場